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Biomedical subjects

F Gauthier

Publications and source records attributed to F Gauthier.

At least 127 records · Page 7Linked to original sources
PubMed1991

Microheterogeneity of rat submaxillary gland kallikrein k10, a member of the kallikrein family.

A tissue-kallikrein-related proteinase present in rat submaxillary glands, which was previously called endopeptidase k, has been further characterized and compared with other members of the kallikrein family. The partial primary structure of this proteinase, now called kallikrein k10, is very similar to that of proteinase B [Kato, H., Nakanishi, E., Enjyoji, K., Hayashi, I., Oh-Ishi, S. & Iwanaga, S. (1987) J. Biochem. (Tokyo) 102, 1389-1404] and T-kininogenase [Xiong, W., Chen. L. M. & Chao, J. (1990) J. Biol. Chem. 265, 2822-2827], but no corresponding gene or mRNA has so far been found. Kallikrein k10 is microheterogeneous due to variable glycosylation of its N-terminal light chain and to variable processing at its kallikrein loop, as shown by endo-beta-N-acetylglucosaminidase F treatment, amino acid sequence analysis and mass spectrometry. The enzymatic properties of the two molecular varieties of kallikrein k10 towards synthetic fluorogenic substrates are not significantly different. Both cleave specifically after Arg residues, but, in contrast to true tissue kallikrein, may accommodate either polar or nonpolar residues at position P2. Kallikrein k10 also differs from tissue kallikrein by its sensitivity to soyabean trypsin inhibitor. Its biological function may therefore differ from that of tissue kallikrein, especially as it does not induce a transient decrease in blood pressure when injected in vivo.

Amino Acid Sequence↗
PubMed1991

Discrimination between rat thiostatin (T-kininogen) and one of its cystatin-like inhibitory fragments by a monoclonal antibody, and localization of the epitope.

A monoclonal antibody (mAb D3) raised against rat thiostatin (T-kininogen) strongly interacted with a fragment, identified as cystatin-like domain 3, which inhibits cysteine proteinases but did not recognize intact, native thiostatin. The antigen-antibody reaction requires cleavage of the single peptide chain of thiostatin in its inter-domain 2-3 region. This mAb can also differentiate between the two molecular varieties of thiostatin, reacting only with immobilized domain 3 from T1 thiostatin, which differs from the T2 variety by only 10 out of 125 residues. mAb D3 did not react with an N-terminally truncated domain 3 of T1 thiostatin prepared by submaxillary gland kallikrein k10 proteolysis. This suggests that the epitope, or an essential part of it, is located on a stretch of 12 residues at the N-terminal of the T1 thiostatin domain 3. This sequence in T1 thiostatin differs from that in T2 thiostatin by four amino acids, two of which are arginyl residues in T1. Chemical modification of these residues located at positions 246 and 250 decreased the reactivity of T1 domain 3 towards the antibody, suggesting that at least one of them is a critical residue of the epitope. Arginine 246 is part of a small disulfide loop between cysteines 245 and 248 which is also necessary for antibody recognition. This antibody does not change the inhibitory properties of purified domain 3 towards papain or rat liver cathepsin L, indicating that the N-terminal part of domain 3 is not involved in inhibition. mAb D3 was used to demonstrate the presence of inhibitory thiostatin fragments in ascites fluid but not in plasma from normal or turpentine-injected rats.

Amino Acid Sequence↗
PubMed1991

Late cholangitis after successful surgical repair of biliary atresia.

Bacterial cholangitis is a frequent complication of successful surgical repair of biliary atresia, occurring in 93% of patients before the age of 1 year, but thought to be rare after 2 years of age. Among 76 children free of jaundice more than 5 years after operation, four presented with late cholangitis (7 to 13.5 years old), consisting of fever, jaundice, and abdominal pain with biochemical features of an inflammatory process and cholestasis. Liver biopsy specimens consistently demonstrated histological features of cholangitis, growth of microorganism, or both. Cholangitis subsided spontaneously in one patient or in response to intravenous administration of antibiotics. Cholangiography consistently demonstrated biliary abnormalities but no definite obstruction to the bilioenteric anastomosis. All the children had good hepatic function 3 weeks to 4 years after the episode of cholangitis. These results suggest that cholangitis may occur several years after surgery but does not seem to alter prognosis.

Acute Disease↗
PubMed1991

Biliary complications after transplantation in children: role of imaging modalities.

Among a series of 140 liver transplantations in children, 21 biliary complications (BC) (15%) are reported. BC were identified from 2 days to 3 months after LT. Positive US findings were present in 20 cases. Cholangiography was obtained by opacification of a surgical drain in 3 cases, per-operatively in 3 and by PTC in 15. Drainage was placed in 9 and balloon dilatation performed in 2. Causes of BC include hepatic artery (HA) thrombosis in 7, HA stenosis in 1, anastomosis stricture in 7, anastomosis kink in 3, mucocele of cystic duct remnant in 2 and sludge in 1. Treatment was surgical in all, but 2 cases were treated percutaneously. There is a great difference in severity of prognosis between complications secondary to HA thrombosis and isolated BC. Role of US in diagnosis and of PTC and interventional radiology in treatment are emphasized.

Adolescent↗
PubMed1991

Apolipoprotein A1 as an early index of protein-energy malnutrition.

Protein-energy malnutrition (PEM) is, together with infectious and parasitic diseases, a major cause of childhood illness in Africa. Diagnosis and treatment of PEM requires an accurate, simple and reliable method of assessing nutritional status from a blood sample. Plasma apolipoprotein (apo A1), prealbumin and albumin were measured in a group of Senegalese children suffering from PEM who had been hospitalized for refeeding, and in a group of control children. Statistical analysis of the results indicated that: (1) Plasma apo A1 was significantly correlated with prealbumin in assessing nutritional status (P less than 0.005 on day 8 of refeeding); (2) plasma apo A1 alone was sufficient for diagnosing and monitoring the dietary treatment of PEM; it was capable of detecting subclinical forms; (3) apo A1 could be used for differential diagnosis of forms of PEM; (4) plasma apo A1 concentration began to increase earlier (94% of control values at day 8) than did prealbumin (73% on day 8). We therefore propose apo A1 as an index of nutritional status in children living in areas where infectious and parasitic diseases are endemic.

Apolipoprotein A-I↗
PubMed1990

Substrate specificity of two kallikrein family gene products isolated from the rat submaxillary gland.

Two proteinases which belong to the tissue kallikrein family were purified from rat submaxillary glands. These proteinases correspond to the products of the RSKG-7 and the rGK8 genes, as shown by the comparison of their partial amino-acid sequence with that deduced from nucleotide sequences. These two proteinases, kallikrein k7 and kallikrein k8, exhibit a marked preference for cleavage after arginyl residues. However, their overall specificities towards synthetic fluorogenic substrates differ significantly from each other and from that of true tissue kallikrein. Kallikrein k7 is strongly inhibited by soybean trypsin inhibitor, whereas kallikrein k8 is not. These data, demonstrating the individual specificity of these kallikrein-like proteinases, suggest that they could be involved in the processing of peptides other than kinins.

Amino Acid Sequence↗
PubMed1990

Simulation of the inhibitory cystatin surface by a synthetic peptide.

An inhibitory dodecameric peptide was designed which tentatively mimics the inhibitory site of cystatin C-like structures. Succinylated and mansylated derivatives were also synthesised and assayed for their inhibiting properties towards papain and rat cathepsins B, H and L. All peptides preferentially inhibit cathepsin L and papain as their naturally occurring inhibitor model. A significant increase in inhibition was obtained after mansylation of the crude peptide with Ki values in the micromolar or 0.1 micromolar range. The use and interest of such peptide inhibitors are discussed.

Amino Acid Sequence↗
PubMed1990

Variability of clinical presentation of hepatic artery thrombosis in pediatric liver transplantation: role of imaging modalities.

Among a series of 90 pediatric liver transplantations, 9 cases of hepatic artery thrombosis (HAT) in 8 patients are reported. All cases were diagnosed in the first two weeks and confirmed angiographically and surgically. Clinical presentation was often unreliable with only 2 cases showing the typical pattern of massive hepatic necrosis. Five cases presented with biliary complications and in 2 cases, HAT was discovered fortuitously on duplex sonography. The role of imaging modalities is emphasized. Duplex sonography is the best non-invasive screening method and we recommend a routine daily examination in the first 2 weeks. CT is the most useful method to assess the extension of liver infarction. PTC remains necessary to evaluate biliary complications and to plan the best therapeutic approach in this devastating event. Two patients died, 2 had to be retransplanted (one patient twice) and are doing well, 2 are on a waiting list for retransplantation and one underwent an emergency surgical arterial desobstruction and is completely asymptomatic.

Child↗
PubMed1990

Long-term outcome after surgery for biliary atresia. Study of 40 patients surviving for more than 10 years.

To define long-term prognosis of children who underwent surgery for biliary atresia, a retrospective study was undertaken in 122 children who underwent one of the Kasaï procedures between 1968 and 1977. Forty of the 122 children (32.7%) were alive after 10 years. Firm hepatomegaly was present in 31 and splenomegaly in 29 children. Serum bilirubin or all liver function tests were normal in 21 and 11 children, respectively; survival rate decreased with the age at operation, but no significant difference was observed in the rate of children surviving with normal serum bilirubin whether they underwent surgery before age 2 months or between 2 and 3 months. Twenty-four had esophageal varices and 15 experienced gastrointestinal bleeding. Normal liver-function tests and absence of portal hypertension were observed in 11 of 122 children. These results indicate that Kasaï's procedures were helpful in a significant proportion of children with biliary atresia who underwent surgery during this period. However, 80% of children who initially underwent surgery with Kasaï's procedures should eventually undergo liver transplantation.

Adolescent↗
PubMed1990

Orthotopic liver transplantation for Byler disease.

Byler disease is a rare form of familial intrahepatic cholestasis that is fatal before puberty. This retrospective study reviewed the results of orthotopic liver transplantation in 14 children with Byler disease using 12 whole-liver grafts and 2 reduced-size grafts. One post-operative death occurred after retransplantation for arterial thrombosis. In the other patients, infectious problems and rejection episodes were the most frequent complications during the postoperative period. In the 13 patients alive, graft function, growth, and quality of life were good after an average follow-up of 17 months without any sign of disease recurrence.

Adolescent↗
PubMed1990

Nutritionally-induced elevation of serum proteinase inhibitors and reduced 3-methylhistidine excretion in the rat.

One group of growing rats was fed ad libitum a low protein and energy diet (PER). A second group was fed a low protein diet (PR). Both these groups showed a gain in weight below that of the control group. A third group was fed a very low protein and energy diet (VPER). A weight gain could also be observed in this group but this gain was lower than those observed in the first two groups. A fourth group that was on a very low protein diet (VPR) gained almost no weight. After 6 weeks a significant reduction in 3-methylhistidine excretion in urine was observed in all the experimental animals with lowest values found in the VPER and VPR groups. Total serum protein levels declined to a certain extent because of the protein and energy restrictions but albumin and transferrin remained largely unaffected. Significantly lower serum concentrations were found only in the VPR group. The rat serum proteinase inhibitors alpha 1-macroglobulin and alpha 1-inhibitor3 decreased when protein and energy were restricted and alpha 1-proteinase inhibitor decreased only in the VPER and VPR groups. alpha 2-macroglobulin and alpha 1-cysteine proteinase inhibitor concentrations increased considerably in the serum of the experimental groups. The results are discussed in relation to the probable role of the latter two inhibitors in the adaptation process when protein and energy were restricted and compared to similar observations recorded in man.

Animals↗
PubMed1990

[Liver transplantation in children. New experience in a Pediatric Surgery unit. Evaluation of the first 18 months' experience].

The authors report an eighteen month experience with orthotopic liver transplantation (OLT) in children in the Pediatric Department of Hospital Bicêtre in Paris, from January 1988 until July 1989. Thirty-eight OLTs including 4 retransplant operations, were performed in 34 children, aged from 7 months to 13 years, 20 of them under the age of 3 years. Biliary atresia was the indication for 22 children. Twenty-eight donors were children. A reduced-size liver was used in 17 cases. The technique for OLT was based on the description by TE Starzl. Surgical complications led to reoperation in 15 cases, mostly in relation to hepatic artery thrombosis (HAT), which occurred in 7 cases: small donor liver was considered to be one of the causative factors. In all but one case of HAT a retransplant was considered; to date it is has been performed in 3 of these children. Thirty-one children have survived, with a mean follow-up of 8 months, all are at home, except for one child at the time of this report. Liver function tests are normal for 22, and moderately altered for 5. For the four remaining children, retransplant is planned for 3 cases and one child has just been retransplanted. The authors emphasise the fact that OLT in small children requires a specialised pediatric environment, particularly as regards intensive care and nursing.

Adolescent↗